1. Field of the Invention
The hybridoma technique of Kohler and Milstein revolutionalized immunology and its applications to many other fields. Exquisitely specific monoclonal antibodies produced in mice and rats are available in virtually unlimited quantities. Recently, there have been reports of the production of human monoclonal antibodies. Human monoclonal antibodies have many advantages over the monoclonal antibodies developed with murine or rat systems, particularly in in vivo diagnosis and therapy. This is a particular concern with in vivo therapy, due to the risk of sensitization with xenoantisera.
Furthermore, the spectrum of the human immune response may be more restricted and therefore useful for the production of monoclonal antibodies to cell surface markers, such as HLA specificities. Also, the isolation of autoimmune monoclonal antibodies and their use as antigens could lead to human monoclonal anti-idiotypic therapy to regulate the responses to autoantigens or transplanted tissue antigens. Finally, humoral responses to infectious disease agents could be exploited to develop useful diagnostic monoclonal antibodies. Despite these provocative advantages, the general applicability of hybridoma techniques to prepare the human monoclonal antibodies has been limited.
2. Description of the Prior Art
EBV containing supernatants have previously been utilized to transform human B cells into cell lines producing polyclonal or monoclonal antibodies against NNP hapten (Rosen et al., Nature (1977) 267:52), TPN hapten (Kozbor et al., Scand. J. Immunol. (1979) 10:187), Rh antigen (Koskimies, Scand. J. Immunol. (1979) 10:371, Boylston et al., ibid (1980) 12:355) Streptococcus A carbohydrate (Steinitz et al., Immunobiology (1979) 156:41) Tetanus toxoid (Zurawski et al., Science (1978) 199:1439), rheumatoid associated IgG (Steinitz et al., Nature (1980) 287:443) and phosphorylcholine (Yoshie and Ono, Immunol. (1980) 56:305). See also Croce et al., Nature (1980) 288:488 and Olsson and Kaplan, PNAS USA (1980) 77:5429 for reports of production of human hybridomas employing cell fusion and monoclonal antibodies from the hybridomas. See also Bird et al., J. Exp. Med. (1981) 154:832 describing EBV activation of human B lymphocytes and Kozbor and Roder, Immunology (1981) 127:1275 describing using EBV for the establishment of monoclonal antibodies against tetanus toxoid.